A porous poly(lactic-co-glycolic acid) scaffold induces innervation in a rabbit model of disc degeneration following annular injury

Long Xin; Guocan Han; Fengdong Zhao; Xing Zhao; Wei Wang; Changyou Gao; ShunwuFan

摘要

BACKGROUND:A degradable poly(lactic-co-glycolic acid)(PLGA) scaffold has been used to construct a degradable porous scaffold.This template can simulate the in vivo microenvironment and promote tissue formation. OBJECTIVE:To observe the histopathological changes during degeneration and regeneration of the intervertebral disc,and to analyze the effects of a PLGA scaffold on nerve fiber ingrowth into the lesion in vivo. DESIGN,TIME AND SETTING:A randomized,controlled animal experiment was performed at the Orthopaedic Laboratory,Clinic Medical Research Institution,Sir Run Run Shaw Hospital,Zhejiang University,from December 2007 to July 2008. MATERIALS:PLGA(China Textile Academy);growth-associated protein-43(Life-span,USA);and protein gene product 9.5 antibody(AbD,United Kingdom) were used in this study. METHODS:Three consecutive segments of the intervertebral disc of thirty-two healthy adult male New Zealand rabbits were exposed,comprising L_(3-4),L_(4-5) and L_(5-6).Experimental intervertebral disc (L_(4-5) and L_(5-6)) models were established by two different methods.In the test(trephine+scaffold) group,a 5-mm deep hole was drilled into the annulus fibrosus using a 3-mm diameter trephine,and the PLGA scaffold was implanted into the hole.In the acupuncture group,the remaining experimental intervertebral disc annulus fibrosus was damaged using a 16G needle at a depth of 5 mm.The L_(3-4) disc served as a control. MAIN OUTCOME MEASURES:Intervertebral disc degeneration was assessed using radiography, magnetic resonance imaging,and histological examination at various time points post-surgery. Nerve fiber ingrowth into the degenerated intervertebral disc was observed using immunohistochemical staining for growth-associated protein-43 and protein gene product 9.5. RESULTS:Compared with the normal controls,the heights of the damaged intervertebral discs were decreased,and T2 signal intensity was decreased in the test and acupuncture groups 2 weeks post-surgery.Intervertebral disc degeneration was faster in the test group than in the acupuncture group.PLGA was coated with newly formed tissue,gradually degraded,and absorbed,and could induce tissue ingrowth deep into the annulus fibrosus.Results of immunohistochemical staining showed that nerve fibers were distributed in newly formed tissue in the test group,and in the superficial layer or surrounding scar tissue in the acupu.cture group. CONCLUSION:A porous PLGA scaffold provides an important biological channel to induce nerve fiber ingrowth deep into the degenerated intervertebral disc.

A porous poly(lactic-co-glycolic acid) scaffold induces innervation in a rabbit model of disc degeneration following annular injury

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